Tamoxifen Resistance Linked to Heightened Growth Factor Signaling

Some estrogen receptor-positive (ER+) breast cancers respond poorly to tamoxifen because of increased growth factor (GF) signaling, according to a team of scientists. The study is published in BMC Medical Genomics in a paper titled “Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer.”

To investigate the differences between those ER+ cancers that respond well to Tamoxifen (luminal-A) and those that do not (luminal-B), the researchers used a computational method of gene-expression analysis called gene set enrichment analysis (GSEA).

They found increased growth factor activation in the gene-expression profiles of nearly 100 luminal-B breast cancer samples. They also showed that treatment with the growth factor heregulin, which induced growth factor signaling in an in vitro model, could overcome tamoxifen-induced cell cycle arrest.

“We propose that activation of GF signaling contributes to this highly proliferative, relatively tamoxifen-insensitive phenotype and that this exists independently of HER2 overexpression,” explains Sherene Loi, from the Peter MacCallum Cancer Centre, Melbourne.